Using molecular genetics as the basis for diagnosis, to assess the phenotype in the family originally described as having dominantly inherited Doyne honeycomb retinal dystrophy (DHRD) linked to chromosome 2p16.
Clinical examination including fluorescein angiography was undertaken in 107 family members. Nine affected patients underwent electroretinography, perimetry, dark adaptometry, color-contrast sensitivity measurement, and autofluorescent fundus imaging.
The disease-associated haplotype used to allocate disease status was based on our further refinement of the DHRD locus to between loci D2S2739 and D2S378. The study identified 50 affected patients. In addition, previously published information on a further 8 individuals was used. The study population represented 6 generations of a 9-generation pedigree.
Three types of deposits were seen: large, soft drusen at the macula and abutting the optic nerve head; small, hard deposits that in some patients radiated from the macula; and autofluorescent deposits. Most younger affected individuals exhibited small hard drusen only at the macula and had normal visual function. Information on 2 patients suggested that DHRD can be a cause of childhood-onset blindness. Advanced disease was associated with severe visual loss and posterior pole atrophy without signs of drusen. Advanced age was not invariably associated with severe visual loss.
Previously identified characteristics of DHRD were confirmed and new features identified. Contrary to previous reports, the constancy and severity of radial (basal laminar) drusen seen clinically are the only features that can be used to differentiate between DHRD and malattia leventinese. The highly variable phenotype suggests that the influence of the DHRD-mutant gene may be modulated by other genetic and/or environmental factors.
Evans K, Gregory CY, Wijesuriya SD, Kermani S, Jay MR, Plant C, Bird AC. Assessment of the Phenotypic Range Seen in Doyne Honeycomb Retinal Dystrophy. Arch Ophthalmol. 1997;115(7):904-910. doi:10.1001/archopht.1997.01100160074012